The fully linked HTML version of this article has now been published.
Development ePress online publication date 21 Apr 2004
doi: 10.1242/dev.01115
Research article
Direct interaction with Hoxd proteins reverses Gli3-repressor function to promote digit formation downstream of Shh
Yuting Chen,
Vladimir Knezevic,
Valerie Ervin,
Richard Hutson,
Yvona Ward,
and
Susan Mackem*
* Author for correspondence (e-mail: smack{at}helix.nih.gov)
Sonic hedgehog (Shh) signaling regulates both digit number and identity, but how different distinct digit types (identities) are specified remains unclear. Shh regulates digit formation largely by preventing cleavage of the Gli3 transcription factor to a repressor form that shuts off expression of Shh target genes. The functionally redundant 5'Hoxd genes regulate digit pattern downstream of Shh and Gli3, through as yet unknown targets. Enforced expression of any of several 5'Hoxd genes causes polydactyly of different distinct digit types with posterior transformations in a Gli3(+) background, whereas, in Gli3 null limbs, polydactylous digits are all similar, short and dysmorphic, even though endogenous 5'Hoxd genes are broadly misexpressed. We show that Hoxd12 interacts genetically and physically with Gli3, and can convert the Gli3 repressor into an activator of Shh target genes. Several 5'Hoxd genes, expressed differentially across the limb bud, interact physically with Gli3. We propose that a varying [Gli3]:[total Hoxd] ratio across the limb bud leads to differential activation of Gli3 target genes and contributes to the regulation of digit pattern. The resulting altered balance between 'effective' Gli3 activating and repressing functions may also serve to extend the Shh activity gradient spatially or temporally.
This article has been cited by other articles:
|
|
|
|
 
V. Fotaki, T. Yu, P. A. Zaki, J. O. Mason, and D. J. Price
Abnormal Positioning of Diencephalic Cell Types in Neocortical Tissue in the Dorsal Telencephalon of Mice Lacking Functional Gli3
J. Neurosci.,
September 6, 2006;
26(36):
9282 - 9292.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Panman, A. Galli, N. Lagarde, O. Michos, G. Soete, A. Zuniga, and R. Zeller
Differential regulation of gene expression in the digit forming area of the mouse limb bud by SHH and gremlin 1/FGF-mediated epithelial-mesenchymal signalling
Development,
September 1, 2006;
133(17):
3419 - 3428.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. D. Capellini, G. Di Giacomo, V. Salsi, A. Brendolan, E. Ferretti, D. Srivastava, V. Zappavigna, and L. Selleri
Pbx1/Pbx2 requirement for distal limb patterning is mediated by the hierarchical control of Hox gene spatial distribution and Shh expression
Development,
June 1, 2006;
133(11):
2263 - 2273.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Li, X. Xu, D. K. Nelson, T. Williams, M. R. Kuehn, and C.-X. Deng
FGFR1 function at the earliest stages of mouse limb development plays an indispensable role in subsequent autopod morphogenesis
Development,
November 1, 2005;
132(21):
4755 - 4764.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. M. Williams, M. E. Williams, J. H. Heaton, T. D. Gelehrter, and J. W. Innis
Group 13 HOX proteins interact with the MH2 domain of R-Smads and modulate Smad transcriptional activation functions independent of HOX DNA-binding capability
Nucleic Acids Res.,
August 8, 2005;
33(14):
4475 - 4484.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Nguyen, A. L. Chokas, B. Stecca, and A. R. i Altaba
Cooperative requirement of the Gli proteins in neurogenesis
Development,
July 15, 2005;
132(14):
3267 - 3279.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Merabet, J. C.-G. Hombria, N. Hu, J. Pradel, and Y. Graba
Hox-controlled reorganisation of intrasegmental patterning cues underlies Drosophila posterior spiracle organogenesis
Development,
July 1, 2005;
132(13):
3093 - 3102.
[Abstract]
[Full Text]
[PDF]
|
|
|
© The Company of Biologists Ltd 2004
